Symptoms of skin aging such as wrinkle, sagging/looseness, pigmentation, depigmentation and thinning of skin and decreasing of skin viscoelasticity have a considerable influence on QOL (Quality of life) of human, particularly women and may become an obstacle on their social lives when the symptoms are severe. Although many symptoms of skin aging were previously believed to develop with advancing age, so-called “physiological aging”, in recent years most of the symptoms of skin aging have been considered to be caused by exposure to ultraviolet rays (so-called photoaging). Exposure of skin to ultraviolet rays causes inflammation followed by phenomena such as dermal tissue destruction and deterioration of fibroblast, resulting in the cosmetic change of face and appearance of skin aging.
On the other hand, along with skin aging, skin scarring such as keloids also has a major influence on patient's QOL, and may become an obstacle on his or her social life depending on its affecting level and affected area (such as face). A scar is formed through a healing process of an injury or the like as described below: that is, skin lesion with an injury resulted from a surgical operation or the like onsets wound healing process including hemorrhage/coagulation phase, inflammation phase and proliferation phase, epidermalization is completed after a given period, and then scar-maturing phase at which scar matures leads to wound healing with scar remained.
During this process, scar including hypertrophic scar, scar contracture, keloids and atrophic scar skin may be formed depending on the conditions such as delay of healing, age of a patient and an affected area. Occasionally conditions such as scar contracture, keloids and atrophic scar skin may occur. Although in many cases hypertrophic change calms down over time, in some cases symptoms such as red flare, pruritus and pain are severe to result in significantly deteriorated patient's QOL for an extended period. Additionally, even if scarring settles down, a wide scar and atrophic scar skin are often left, in any case of which patient's QOL may be often deteriorated for a long period.
As stated above, skin aging and skin scarring cause not only patient's cosmetic and functional problems but also social problems including patient's QOL.
Patent Document 1 discloses that local application or topical spraying of basic fibroblast growth factor (bFGF) or platelet derived growth factor (PDGF) etc. enhances regeneration/reconstruction of living tissue of animals and plants and shows an effect/efficacy on a treatment of skin ulcer and bedsore. Furthermore, Patent Documents 2 and 3 disclose that administration of bFGF by dermal or subcutaneous injection enhances skin regeneration and skin wound healing.
However, when an active ingredient is to be administered to an affected area, application or spraying of a liquid preparation containing the active ingredient cannot allow it to remain and penetrate adequately, not to result in sufficient therapeutic effect. An intracutaneous or subcutaneous injection cause a considerable pain to a patient, and has such problems on a clinical application that a physician is required to have a trained skill to evenly inject the injection solution into the dermis and epidermis/dermis junctional region and, in addition, that unevenness of a drug in the tissue at the time of injection becomes evident as uneven level of activity at the time of production of effects. Furthermore, a liquid preparation used for application or subcutaneous injection has poor preservation stability and the ingredient is so susceptible to time degradation that it is difficult to store and handle it.
On the other hand, microneedle type formulations have been studying as a pharmaceutical technology to administer an objective substance transdermally. The microneedles are so tiny that subjects have no pain even when the needles are inserted into the skin. Self-dissoliving microneedles containing an objective substance are inserted through the skin into the body, and the microneedles then dissolve by themselves to result in the objective substance taken into the body.
For example, Patent Document 4 discloses the formation of microneedles using a bio-soluble and thread-forming polymer substance as a base. Patent Document 5 discloses that a microneedle is separated into a part to be inserted into the body and a part to be pushed to improve bioavailability of an objective substance contained in above mentioned microneedle, wherein the objective substance is retained only in the part to be inserted to the body.
In addition, Patent Documents 4 and 5 disclose a microneedle assembly formulation with a plurality of above microneedles formed on a platform such as adhesive skin patch sheet. Patent Document 6 discloses a microneedle assembly formulation with a porous substrate and the production method thereof.
However, the optimal prescription, administration condition and efficiency when a microneedle assembly formulation is used for prevention or treatment of skin aging or treatment of skin scar have not been known yet.
[Patent document 1] Japanese Patent Laid-open Publication No. 2002-249498
[Patent document 2] Japanese Patent Laid-open Publication No. 2003-342194
[Patent document 3] International Publication No. WO 2009/119073
[Patent document 4] International Publication No. WO 2006/080508
[Patent document 5] International Publication No. WO 2009/066763
[Patent document 6] Japanese Patent Laid-open Publication No. 2011-12050